scholarly journals Identification of Enhancer RNA CDK6-AS1 as a Potential Novel Prognostic Biomarker in Gastric Cancer

2021 ◽  
Author(s):  
Shifeng Yang ◽  
Xiaoming Zou ◽  
Hao Yang ◽  
Jiacheng Li ◽  
Ange Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Gene ◽  
Drug Sensitivity ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Driver Genes ◽  
Pathway Enrichment ◽  
Enhancer Rna ◽  
Oncogenic Pathway ◽  
Pan Cancer

Abstract Background:The aim of this study was to confirm enhancer RNAs (eRNAs) in gastric cancer and its clincial utility. Methods:We used cox survival analysis and relevance analysis to identify the candidate eRNAs in gastric cancer. Moreover, we performed GO and Reactome pathway enrichment to found the potential functions of eRNAs.Correlation between eRNA, tumor-infiltrating immune cells and drug sensitivity was then analyzed. Results: CDK6-AS1 may serve as a poor independent prognostic biomarker candidate in gastric cancer with positive correlation with its target gene CDK6. Low CDK6-AS1 expression group showed more frequent mutated driver genes than high expression ones. Moreover, CDK6-AS1 is involved in key oncogenic pathway as cell cycle and RNA transcription. CDK6-AS1 also shows dysregulations and associations with prognosis at pan-cancer level. This eRNA may also associated with immune cell infiltration and drug sensitivity. Conclusion:CDK6-AS1 may be a potential prognostic biomarker for gastric cancer, predict chemotherapeutic drugs sensitivity of gastric cancer.

scholarly journals Effects of Inflammation on the Immune Microenvironment in Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Weidan Zhao ◽  
Mingqing Liu ◽  
Mingyue Zhang ◽  
Yachen Wang ◽  
Yingli Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Inflammatory Response ◽  
Immune Cell ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Cancer Prognosis ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Immune Factor

BackgroundChronic inflammation and immune cell dysfunction in the tumor microenvironment are key factors in the development and progression of gastric tumors. However, inflammation-related genes associated with gastric cancer prognosis and their relationship with the expression of immune genes are not fully understood.MethodIn this study, we established an inflammatory response model score called “Riskscore”, based on differentially expressed genes in gastric cancer. We used Survival and Survminer packages in R to analyze patient survival and prognosis in risk groups. The survival curve was plotted using the Kaplan–Meier method, and the log-rank test was used to assess statistical significance, and we performed the ROC analysis using the R language package to analyze the 1-, 3-, and 5-year survival of patients in the GEO and TCGA databases. Single-factor and multi-factor prognostic analyses were carried out for age, sex, T, N, M, and risk score. Pathway enrichment analysis indicated immune factor-related pathway enrichment in both patient groups. Next, we screened for important genes that are involved in immune cell regulation. Finally, we created a correlation curve to explore the correlation between Riskscore and the expression of these genes.ResultsThe prognosis was significantly different between high- and low-risk groups, and the survival rate and survival time of the high-risk group were lower than those of the low-risk group. we found that the pathways related to apoptosis, hypoxia, and immunity were most enriched in the risk groups. we found two common tumor-infiltrating immune cell types (i.e., follicular helper T cells and resting dendritic cells) between the two risk groups and identified 10 genes that regulate these cells. Additionally, we found that these 10 genes are positively associated with the two risk groups.ConclusionFinally, a risk model of the inflammatory response in gastric cancer was established, and the inflammation-related genes used to construct the model were found to be directly related to immune infiltration. This model can improve the gastric cancer prognosis prediction. Our findings contribute to the development of immunotherapy for the treatment of gastric cancer patients.

scholarly journals A Pan-cancer Analysis of Thioredoxin-interacting Protein as an Immunological and Prognostic Biomarker

2022 ◽  
Author(s):  
Xuxue Guo ◽  
Mei Huang ◽  
Haonan Zhang ◽  
Qianhui Chen ◽  
Ying Hu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Prognostic Biomarker ◽  
Redox Homeostasis ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Inflammasome Activation ◽  
Post Translational Modification ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Pan Cancer

Abstract BackgroundThe critical role of thioredoxin-interacting protein (TXNIP) in cellular sulfhydryl redox homeostasis and inflammasome activation is already widely known, however, no pan-cancer analysis is currently available. MethodsWe thus first explored the potential roles of TXNIP across thirty-three tumors mainly based on The Cancer Genome Atlas and Gene Expression Omnibus datasets. ResultsTXNIP is lowly expressed in most cancers, and distinct associations exist between TXNIP expression and the prognosis of tumor patients. TXNIP expression was associated with tumor mutational burden, microsatellite instability, mismatch repair genes, tumor infiltrating immune cell abundance as well as cancer-associated fibroblasts. Moreover, ubiquitin mediated proteolysis, protein post-translational modification and other related pathways were involved in the functional mechanisms of TXNIP. ConclusionsOur first pan-cancer study offers a relatively comprehensive understanding of the carcinostatic roles of TXNIP across different tumors. And this molecule may be considered as a potential immunological and prognostic biomarker.

scholarly journals Comprehensive Analysis to Identify SPP1 as a Prognostic Biomarker in Cervical Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Kaidi Zhao ◽  
Zhou Ma ◽  
Wei Zhang
Keyword(s):  
Cervical Cancer ◽  
Roc Curve ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
R Package ◽  
Cancer Data ◽  
Immune Infiltration ◽  
Pan Cancer ◽  
Geo Database

Background:SPP1, secreted phosphoprotein 1, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. Previous studies have proven SPP1 overexpressed in a variety of cancers and can be identified as a prognostic factor, while no study has explored the function and carcinogenic mechanism of SPP1 in cervical cancer.Methods: We aimed to demonstrate the relationship between SPP1 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. Next, we validated SPP1 expression of cervical cancer in the Gene Expression Omnibus (GEO) database, including GSE7803, GSE63514, and GSE9750. The receiver operating characteristic (ROC) curve was used to evaluate the feasibility of SPP1 as a differentiating factor by the area under curve (AUC) score. Cox regression and logistic regression were performed to evaluate factors associated with prognosis. The SPP1-binding protein network was built by the STRING tool. Enrichment analysis by the R package clusterProfiler was used to explore potential function of SPP1. The single-sample GSEA (ssGSEA) method from the R package GSVA and TIMER database were used to investigate the association between the immune infiltration level and SPP1 expression in cervical cancer.Results: Pan-cancer data analysis showed that SPP1 expression was higher in most cancer types, including cervical cancer, and we got the same result in the GEO database. The ROC curve suggested that SPP1 could be a potential diagnostic biomarker (AUC = 0.877). High SPP1 expression was associated with poorer overall survival (OS) (P = 0.032). Further enrichment and immune infiltration analysis revealed that high SPP1 expression was correlated with regulating the infiltration level of neutrophil cells and some immune cell types, including macrophage and DC.Conclusion:SPP1 expression was higher in cervical cancer tissues than in normal cervical epithelial tissues. It was significantly associated with poor prognosis and immune cell infiltration. Thus, SPP1 may become a promising prognostic biomarker for cervical cancer patients.

scholarly journals ITGA5 Is a Prognostic Biomarker and Correlated with Immune Infiltration In Gastrointestinal Cancers

2020 ◽  
Author(s):  
Hai Zhu ◽  
Gang Wang ◽  
Haixing Zhu ◽  
Aman Xu
Keyword(s):  
Gastric Cancer ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Th2 Cells ◽  
Integrin Subunit ◽  
Expression Levels ◽  
Immune Infiltration

Abstract Background: Integrin Subunit Alpha 5 (ITGA5) belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal (GI) tumors remain unclear.Methods: The expression levels of ITGA5 were detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan–Meier plotter, Gene Expression Profiling Interactive Analysis 2(GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER and immunohistochemistry (IHC) staining were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape.Results: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of GI tumors. In addition, ITGA5 expression levels was significantly associated with tumor purity and immune infiltration levels of different immune cells in GI tumors. Interestingly, Immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 were mainly involved in “integrin mediated signaling pathway”, “leukocyte migration”, “cell-substrate adhesion”.Conclutions: our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in GI tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.

scholarly journals Glutamine Metabolism Regulators Associated with Cancer Development and the Tumor Microenvironment: A Pan-Cancer Multi-Omics Analysis

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1305
Author(s):  
Jingwen Zou ◽  
Kunpeng Du ◽  
Shaohua Li ◽  
Lianghe Lu ◽  
Jie Mei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Drug Sensitivity ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Molecular Networks ◽  
Cancer Types ◽  
Pan Cancer

Background: In recent years, metabolic reprogramming has been identified as a hallmark of cancer. Accumulating evidence suggests that glutamine metabolism plays a crucial role in oncogenesis and the tumor microenvironment. In this study, we aimed to perform a systematic and comprehensive analysis of six key metabolic node genes involved in the dynamic regulation of glutamine metabolism (referred to as GLNM regulators) across 33 types of cancer. Methods: We analyzed the gene expression, epigenetic regulation, and genomic alterations of six key GLNM regulators, including SLC1A5, SLC7A5, SLC3A2, SLC7A11, GLS, and GLS2, in pan-cancer using several open-source platforms and databases. Additionally, we investigated the impacts of these gene expression changes on clinical outcomes, drug sensitivity, and the tumor microenvironment. We also attempted to investigate the upstream microRNA–mRNA molecular networks and the downstream signaling pathways involved in order to uncover the potential molecular mechanisms behind metabolic reprogramming. Results: We found that the expression levels of GLNM regulators varied across cancer types and were related to several genomic and immunological characteristics. While the immune scores were generally lower in the tumors with higher gene expression, the types of immune cell infiltration showed significantly different correlations among cancer types, dividing them into two clusters. Furthermore, we showed that elevated GLNM regulators expression was associated with poor overall survival in the majority of cancer types. Lastly, the expression of GLNM regulators was significantly associated with PD-L1 expression and drug sensitivity. Conclusions: The elevated expression of GLNM regulators was associated with poorer cancer prognoses and a cold tumor microenvironment, providing novel insights into cancer treatment and possibly offering alternative options for the treatment of clinically refractory cancers.

scholarly journals TUG1 acts as a biomarker to predict the relapse of gastric cancer after endoscopic submucosal dissection (EMR)

2021 ◽  
Author(s):  
Jianhua Wang ◽  
Yanping Hao ◽  
Tingting Yu ◽  
Liang Han ◽  
Ping Xu
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Target Gene ◽  
Prognostic Biomarker ◽  
Rank Test ◽  
Log Rank Test ◽  
Mtt Assays ◽  
Free Rate

IntroductionMiR-382 was reported to act as a prognostic biomarker for the relapse of gastric cancer (GC) after endoscopic mucosal resection (EMR). In addition, TUG1 was reported to regulate cell proliferation via sponging miR-382. Therefore, in this study, we aimed to investigate the value of TUG1 in predicting post-EMR relapse of GC.Material and methodsLog rank test was utilized to analyze relapse-free rate and validate the prognostic value of TUG1 in predicting post-EMR GC relapse. Real-time PCR, Western Blot and luciferase assays were performed to clarify the regulatory relationships among TUG1, miR-382 and CD44, thus establishing a TUG1/miR-382/CD44 signaling pathway. Moreover, MTT assays were conducted to observe the effect of TUG1 on cell proliferation and post-EMR GC relapse.ResultsThe AUC of the high TUG1 expression group was obviously smaller than that of the low TUG1 expression group, which indicated that the expression of TUG1 could be used as a prognostic biomarker to predict the risk of post-EMR GC relapse. In addition, a negative correlation was found between miR-382 expression and the expression of its endogenous competing RNA TUG1. Furthermore, miR-382 was shown to inhibit the expression of its target gene CD44. Finally, a TUG1/miR-382/CD44 signaling pathway was established and was implicated in post-EMR recurrence of GC, and the overexpression of TUG1 was shown to promote the proliferation of GC cells.ConclusionsReduced expression of TUG1 could inhibit the proliferation of GC cells and increase the expression of miR-382, which in turn down-regulated CD44 expression and lowered the risk of post-EMR GC relapse.

scholarly journals INHBA is A Novel Prognostic Biomarker And Correlated With Immune Infiltrates In Gastric Cancer

2021 ◽  
Author(s):  
Weifeng Yu ◽  
Zishao Zhong ◽  
Guihua He ◽  
Wang Zhang ◽  
Zhenhao Ye ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Extracellular Matrix ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Curve Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Collagen Formation ◽  
Matrix Organization ◽  
The Impact

Abstract Background: Inhibin subunit beta A (INHBA) is reportedly a potential prognostic biomarker for a variety of cancers. However, its role in gastric cancer (GC) remains elusive. Methods: The expression of INHBA in GC and healthy tissues based on the data obtained from the UCSC Xena database. Logistic regression and Cox regression was performed to explore the correlation between clinical indicators and INHBA expression. Kaplan–Meier curve analysis was performed to assess the impact of INHBA expression on overall survival(OS). In addition, Received operating characteristic curve analysis was implied to clarify the diagnostic role of INHBA in GC. Functional analyses were conducted to explain the potential functions and enrichment pathways for INHBA. TIMER and GEPIA databases were used to calculate the confidence between INHBA and immune cell infiltration in GC. Results: INHBA was upregulated in GC(P < 0.001) and associated with a poor prognosis(P = 0.037). INHBA expression was an independent risk factor for OS(P = 0.004). Additionally, INHBA was a potential diagnostic marker in GC(AUC=0.961) and it was associated with extracellular matrix organization, response to growth factor, and cell-substrate adhesion. Tumor-associated signaling pathways, such as Wnt, Hippo, and p53, were associated with INHBA. Reactome pathways, such as collagen formation and extracellular matrix organization, were significantly enriched. Moreover, high INHBA expression displayed a strong correlation with immune cell infiltration, especially with macrophage infiltration in GC.Conclusions: INHBA could be a potential prognostic biomarker for GC and may drive the abnormal activity of critical cancer-associated pathways, potentially contributing to immune cell infiltration to promote GC development and becoming a new drug target for targeted GC therapies.

scholarly journals KIF18B is a Prognostic Biomarker and Correlates with Immune Infiltrates in Pan-Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Meng-jun Qiu ◽  
Qiu-shuang Wang ◽  
Qiu-ting Li ◽  
Li-sheng Zhu ◽  
Ya-nan Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Tumor Mutation Burden ◽  
R Language ◽  
Normal Tissues ◽  
Expression Difference ◽  
Mutation Burden ◽  
Cancer Types ◽  
Pan Cancer

Background: Cancer is one of the deadliest diseases at present. Although effective screening and treatment can save lives to a certain extent, our knowledge of the disease is far from sufficient. KIF18B is a member of the kinesin-8 superfamily and plays a conserved regulatory role in the cell cycle. KIF18B reportedly functions as an oncogene in some human cancers, but the correlations between KIF18B and prognosis and immune-infiltrates in different cancers remain unclear.Methods: Data were collected from the TCGA, GTEx, CCLE, TIMER, and GSEA databases. The expression difference, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs), tumor microenvironment (TME), immune cell infiltration, and gene co-expression of KIF18B were analyzed using the R language software.Results: KIF18B was widely upregulated in cancers, compared with normal tissues, and high KIF18B expression was associated with unfavorable prognoses. TMB, MSI, MMRs, and DNA methylation correlated with KIF18B dysregulation in cancers. KIF18B correlated closely with tumor immunity and interacted with different immune cells and genes in different cancer types.Conclusion: KIF18B could be used as a prognostic biomarker for determining prognosis and immune infiltration in pan-cancer.

PDGFRB is a potential prognostic biomarker and correlated with immune infiltrates in gastric cancer

2021 ◽  
pp. 1-14
Author(s):  
Baohong Liu ◽  
Xingxing Xiao ◽  
Ziqin Lin ◽  
Yongliang Lou ◽  
Lingling Zhao
Keyword(s):  
Gastric Cancer ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Growth Factor Receptor ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Immune Cell Infiltration ◽  
Clinicopathologic Characteristics ◽  
Mortality And Morbidity ◽  
Poor Outcomes

Gastric cancer (GC) is a common cancer with high mortality and morbidity rates worldwide. Although medical and surgical treatments have improved, the mechanisms of the progression of GC remain unclear. Platelet-derived growth factor receptor-β (PDGFRB) plays a pivotal role in angiogenesis and tumor cell proliferation and has been suggested as a prognostic marker of cancer. This study aimed to explore the relationship of PDGFRB expression with clinicopathologic characteristics, immune cell infiltration status, and prognosis in GC. In this study, we visualized the expression and prognostic values of PDGFRB in GC using the Oncomine, UALCAN, GEPIA, and Kaplan-Meier Plotter databases. And then we explored the potential relationships between PDGFRB expression and the levels of immune cell infiltration using the TIMER, GEPIA databases and CIBERSORT algorithm. Furthermore, LinkedOmics analysis was performed to explore the functions for PDGFRB. The results showed close correlations between PDGFRB and immune cell infiltration especially M2 Macrophage infiltration in GC. High PDGFRB expression was related to poor outcomes in GC. High PDGFRB expression can negatively affect GC prognosis by promoting angiogenesis and modulating the tumor immune microenvironment. These results strongly suggest that PDGFRB can be used as a prognostic biomarker of GC and provide novel insights into possible immunotherapeutic targets.

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